RESUMO
The development of sustainable analytical methodologies that minimize hazards, waste generation, and energy consumption has become crucial. This study introduces pioneering greenâblue-white approaches for the simultaneous quantification of montelukast sodium (MLK) and fexofenadine hydrochloride (FEX) in combination formulations. The first approach employs an ultra-performance liquid chromatographic method (UPLC) with a green micellar mobile phase of 0.02 M sodium dodecyl sulfate and 10% 1-pentanol (65:35%). The method demonstrated excellent resolution, peak symmetry, and a short analysis time, with retention times of 3.53 min for MLK and 1.67 min for FEX. The MLK and FEX linearities were 1-260 and 1.2-312 µg/mL, respectively. The second approach involves complementary built-in spectroscopic techniques (second derivative, third derivative, and ratio difference methods) using water as a solvent, providing a green, simple, low-cost alternative in laboratories where expensive chromatographic devices may not be readily available. The MLK and FEX linearities were 3-50 and 3-60 µg/mL, respectively. All methods were comprehensively validated and showed satisfactory results. The proposed methods demonstrated excellent linearity (r2 ≥ 0.9990), accuracy (recovery 98.5-101.5%), and precision (RSD ≤ 2%) across wide concentration ranges. A multifaceted evaluation was conducted to assess the environmental sustainability, real-world applicability, and economic viability of the proposed methods in comparison with previously reported techniques. This comprehensive assessment leveraged several state-of-the-art tools, including NEMI, ComplexGAPI, AGREE, ESA, BAGI, and RGB12. The suggested approaches exhibited favorable quadrant profiles in the NEMI and ComplexGAPI assessments, coupled with higher AGREE scores (0.90, 0.86) than reported (0.62, 0.74, 0.75, 0.69, 0.74, 0.74, and 0.75), in addition to higher ESA score (88, 92) than reported (75, 84, 85, 79, 82, 82, and 83), collectively affirming their environmentally friendly credentials. Moreover, we embraced the innovative notions of 'blueness' and 'whiteness' assessment by harnessing the recently formulated BAGI and RGB12 algorithms. The higher BAGI score (90, 82.5) than reported (72.5, 70, 70, 67.5, 67.5, 67.5, and 72.5), confirmed the excellent real-world applicability of the proposed methods, while the notable RGB12 indices (89.8, 88.1) than reported (67.8, 72.8, 71.5, 67.1, 73.7, 70.3, and 73.2), validated their cost-effectiveness and overall sustainability, contributing to an eco-friendly future for quality control processes.
RESUMO
Isoxsuprine (ISX) is widely used for cerebral and peripheral vascular diseases. A comparative study was held among different multivariate calibration models for selective determination of a complex mixture of Isoxsuprine and four of its toxic photothermal degradation products that impair kidney and liver functions. The Partial Least Squares (PLS) and Artificial Neural Network (ANN) models were applied on the specific spectrum and on selected wavelengths using genetic algorithm (GA) technique as an efficient variable selection tool. The effect of GA on the model construction and performance was evaluated. The multilevel multifactor experimental design was adopted for the construction of the calibration set. Optimized parameters were used for the development of the different models. The performances of the developed models were assessed by predicting the concentration of eight different mixtures composing the validation set. Results were compared to one another and to the official method using one-way ANOVA statistical test to assure the validity of the constructed models. The lower chance of overfitting offered by ANN minimized the RMSEP relative to the PLS. On the other hand, the application of GA prior to model implementation affected the number of latent variables the prediction ability of both PLS and ANN models. The validated models were successfully applied as stability indicating assay methods for the selective determination of ISX and its photothermal degradation products in ISX raw material and market formulations.